The clinical characteristics and related factors of tremor in patients with epilepsy

Abstract

Tremor is frequently observed in patients with epilepsy (PWE), which is generally attributed to the side-effect of antiepileptic drugs (AEDs) particularly valproate (VPA) with largely unknown mechanisms. The study aimed to assess the clinical features and related factors of tremor in PWE with tremor. Methods: PWE with tremor and a control group of age-and sex-matched PWE without tremor were enrolled. Detailed demographic and clinical information for each individual was recorded. PWE with tremor were evaluated by The Clinical Rating Scale for Tremor (CRST) and Tremor Related Activities of Daily Living (TRADL) questionnaire. Results: 132 individuals were enrolled, which including sixty-six (36 males) PWE with tremor with mean age of 33 years and epilepsy duration of 12.5 years. Tremor was postural in all, with median duration of four and one year from diagnosis and AED treatment to the onset of tremor respectively. The upper limbs were predominantly affected. VPA had been used in 62 (93.9%) PWE with tremor compared to 31 (47.0%) PWE without tremor (P < 0.001). The total CRST score was significantly associated with epilepsy duration and maximum VPA dosage (B = 0.30, p < 0.001; B = 0.32, p = 0.013). Patients with VPA dosage over 17.05 mg/kg/d might be more vulnerable to develop tremor. Conclusions: PWE with tremor were more frequently treated with VPA, however, tremor was mild in most without any functional impairment. Epilepsy duration and maximum VPA dosage were important factors of tremor severity, suggesting mechanisms underlying tremor in PWE may be an elaborate interplay of AEDs and disease itself.

Transversal investigation of the risk of valproic-acid-induced tremor in a secondary epilepsy center: clinical, neuroimaging, and genetic factors

“…Similar to conclusions of many previous studies, we found that the most prominent risk factors for VPAinduced tremor included VPA usage factors, including treatment duration, daily dosage, and formulations [3,4,[8][9][10]. In our present study, the VPA therapy duration of the tremor group was longer than that of the non-tremor group (p=0.008), and durations of beyond 12 or 24 months increased the incidence of tremor, which is consistent with a recent study demonstrating that the median time from medication to tremor appearance was one year (range of one month to 30 years) [9]. The time from therapy to tremor appearance has been reported to vary from one to 12 months across different cohorts [3,4,32], which might be ascribed to small sample sizes and diverse evaluation methods.…”

“…In our present study, we found that 20.2% of subjects in the tremor group had a family history, whereas only 3.5% of subjects presented with a positive family history in the non-tremor group, indicating that a positive genetic background increases the risk of VPA-induced tremor. Additionally, in our cohort, women were more likely to suffer from VPA-induced tremor, which is consistent with findings from limited studies using scales to measure tremor severity that indicated that women had higher scores in the Clinical Rating Scale for Tremor (CRST) [9,10].…”

“…For the clinical risk factors, the commonly detected risk factors for VPA-induced tremor included VPA therapy duration and daily dosage of VPA, whereas unrelated factors included seizure types, disease duration, abnormalities in neuroimaging/EEGs, the findings of which are similar to those of previous studies [3,4,[8][9][10].…”

“…For example, more sensitive measurements-such as via accelerometers and variable-capacitance transducers-have been shown to enable earlier detection of otherwise undetectable tremors [3,4]. Prior studies have also indicated that tremors usually occur when the daily VPA dosage is over 750 mg, 1,000 mg [3,4], or 17.05 mg/kg [9]. In our present study, the incidence of tremor was increased only when the daily dosage exceeded 1,000 mg; we hypothesize that our exclusion of patients taking less than 500 mg/day of VPA might be responsible for our higher cut-off value.…”

“…Furthermore, lower concentrations of dopamine and norepinephrine were correlated with VPA-induced tremor [8]. Another single-center study indicated that a long duration of epilepsy and a high-daily VPA dosage were risk factors for tremor, whereas gender was not [9]. On the contrary, another study found that women suffered more from VPA-induced tremor [10].…”